STIMULI-SENSITIVE PARTICLES FOR DRUG DELIVERY - Biologically-Responsive Hybrid Biomaterials - page 166

may occur, yielding dead polymers. One key advantage of RAFT polymerization
is that the polymer retains the active functionality, the thiocarbonylthio group,
which can be reactivated and used to build block, star-shaped, or more complex
polymer architectures. [44-46] For example, Covertine et al. synthesized a series
of diblock co-polymers composed of a positively-charged block of DMAEMA
and a second endosomolytic block composed of DMAEMA and PAA in roughly
equimolar ratios together with BMA as carriers for model nucleic acids using
RAFT polymerization techniques. These polymers proved to be sharply
hemolytic at endosomal pH values particularly those with high BMA content.
They successfully condensed siRNA into 80-250 nm particles with slightly
positive Zeta potentials that proved to knock down GAPDH expression in
Hela cells in a trend that followed their hemolytic activity. [47] This clearly
demonstrates the potential of RAFT polymerization in developing well-
controlled polymer compositions for drug delivery.
2.2. Atom transfer radical polymerization (ATRP) technique
The term “atom transfer radical polymerization” was coined by Matyjeszewski in
1995 to describe the use of metal catalysts in combination with aromatic ligands
to yield well-controlled polymer structures with narrow molecular weight
distributions [48]. This mechanism of reaction involves the transfer of a halogen
atom (X) from the dormant polymer chain to a metal catalyst yielding an active
chain end (a radical; P·) that can add monomer units to the polymer chain
through the propagation step (Figure 7). The selected catalyst in this reaction
consists of a transition metal and a halogen. The transition metal (e.g. copper)
has two oxidation states separated by one electron step and can strongly bind to a
multidentate ligand forming a complex. The halogen, typically bromine or
chlorine, should be able to migrate rapidly between the growing polymer chain
and the catalyst [48]. One of the limitations of ATRP is the reaction intolerance
to carboxylic acid and other ionic groups that can react with the catalyst and
Fig. 7. Schematic drawing showing the mechanism of atom transfer radical polymerization
(ATRP).